期刊
JOURNAL OF HAZARDOUS MATERIALS
卷 430, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jhazmat.2022.128368
关键词
Fine particulate matter; Cardiovascular disease; Adverse outcome pathway; Reactive oxygen species; Mitochondria dysfunction
资金
- National Key Research and Develop-ment Program of China, China [2017YFC0211600, 2017YFC0211602, 2017YFC0211606]
- National Natural Science Foundation of China, China [91943301, 92043301]
- Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education, China [KZ202110025040]
The review utilizes the Adverse Outcome Pathway (AOP) framework to illustrate the causal mechanistic relationships of PM2.5-triggered cardiovascular toxicity, highlighting the need for further research in exploring new markers for the safety assessment of PM2.5-induced cardiovascular toxicity.
Fine particulate matter (PM2.5) exposure is a major threat to public health, and is listed as one of the leading factors associated with global premature mortality. Among the adverse health effects on multiple organs or tissues, the influence of PM2.5 exposure on cardiovascular system has drawn more and more attention. Although numerous studies have investigated the mechanisms responsible for the cardiovascular toxicity of PM2.5, the various mechanisms have not been integrated due to the variety of the study models, different levels of toxicity assessment endpoints, etc. Adverse Outcome Pathway (AOP) framework is a useful tool to achieve this goal so as to facilitate comprehensive understanding of toxicity assessment of PM2.5 on cardiovascular system. This review aims to illustrate the causal mechanistic relationships of PM2.5-triggered cardiovascular toxicity from different levels (from molecular/cellular/organ to individual/population) by using AOP framework. Based on the AOP Wiki and published literature, we propose an AOP framework focusing on the cardiovascular toxicity induced by PM2.5 exposure. The molecular initiating event (MIE) is identified as reactive oxygen species generation, fol-lowed by the key events (KEs) of oxidative damage and mitochondria dysfunction, which induces vascular endothelial dysfunction via vascular endothelial cell autophagy dysfunction, vascular fibrosis via vascular smooth muscle cell activation, cardiac dysregulation via myocardial apoptosis, and cardiac fibrosis via fibroblast proliferation and myofibroblast differentiation, respectively; all of the above cardiovascular injuries ultimately elevate cardiovascular morbidity and mortality in the general population. As far as we know, this is the first work on PM2.5-related cardiovascular AOP construction. In the future, more work needs to be done to explore new markers in the safety assessment of cardiovascular toxicity induced by PM2.5.
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